Protective effect of bicyclol against pulmonary fibrosis via regulation of microRNA-455-3p in rats

Abstract

Idiopathic pulmonary fibrosis (IPF), a chronic, progressive and irreversible disease, needs long-term treatment. Bicyclol was found to play a great role in pulmonary fibrosis, and the present study is to explore how bicyclol affects IPF with the involvement of microRNA-455-3p (miR-455-3p) and Bax. Bleomycin (BLM) was used to induce the IPF model in Sprague-Dawley rats to detect the expression of miR-455-3p, Bax, and B-cell lymphoma factor 2 (Bcl-2). Moreover, to further investigate the mechanisms of bicyclol, the BLM-induced fibrotic cell model was used after the lung epithelial cells HPAEpiC received miR-455-3p knockout treatment. The rats were then treated with vehicle and bicyclol, respectively. The apoptosis of fibrotic cells and Bax/Bcl-2 were identified. Inhibition function of bicyclol was optimal at a dose of 150 mg/kg. Bicyclol inhibited cell apoptosis and reduced Bax/Bcl-2 expression in rats. miR-455-3p could potentially bind to Bax gene. Bicyclol reduced the levels of methylenedioxyamphetamine, superoxide dismutase, and glutathione in rat lung tissue, inhibited the apoptosis of rats with IPF and upregulated miR-455-3p expression. In vitro studies showed that bicyclol significantly promoted miR-455-3p expression in HPAEpiC fibrosis. Bicyclol inhibited fibrosis-induced apoptosis of HPAEpiC in alveolar epithelial cells through promoting miR-455-3p, which inhibited Bax expression in IPF. Bicyclol may suppress the apoptosis of alveolar epithelial cells by upregulating miR-455-3p. This study laid a theoretical foundation for further understanding of IPF and searching for new molecular therapeutic targets.